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Query: UMLS:C0018133 (graft-versus-host disease)
18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With donor and recipient matched at the major histocompatibility complex (MHC) locus, peripheral lymphoid tissue transplantation can be carried out without producing a graft-versus-host reaction or graft-versus-host disease (GVHD), thus correcting profound T cell immunodeficiencies of neonatally thymectomized mice. This analysis set the stage for clinical application of bone marrow transplantation (BMT) to provide for the first time cure of a human disease. With successful BMT, we cured immunologic deficiencies of a patient with XL severe combined immunodeficiency; thereafter we were the first to employ BMT to cure aplastic anemia. BMT regularly corrects immune and hematologic deficiencies caused by fatal irradiation without producing GVHD if the bone marrow (BM) used for the transplants has been purged of postthymic T cells. Over two decades in conjunction with Ikehara et al., we have shown that lethal total body irradiation (TBI) plus allogeneic BMT prevents or cures many organ-specific and systemic experimental autoimmune diseases. Animal models successfully treated by BMT include type I diabetes in nonobese diabetes (NOD) mice, type II diabetes in insulin-insensitive, glucose intolerant, diabetes mellitus (KK/Ay) mice, and autoimmune lupus erythematosus (LE) and glomerulonephritis in New Zealand Black x New Zealand White first generation hybrid (NZB x NZW)F1 females. El-Badri extended Ildstad's original research showing a high frequency of survival with a normal functioning immune system after stable mixed chimerism is produced by mixed BMT in C57BL/6 (normal long-lived black strain) mice transplanted with T cell-depleted marrow (TCDM) from BALB/c ("normal" long-lived strain) allogeneic donors and C57BL/6 syngeneic donors. We showed that osteoblasts act as facilitator cells for allogeneic BMT and promote engraftment of allogeneic hematopoietic stem cells. Wang et al. then showed that the autoimmunities and fulminating renal disease of BXSB (C57BL x SB cross and selective lupus-like systemic autoimmunity) male mice was prevented and could be cured by transplantation using TCDM from both BALB/c (resistant) and BXSB (susceptible) strains given to BXSB recipients after lethal TBI. This treatment produced mixed BMT and a stable mixed chimerism, increased longevity, corrected all manifestations of autoimmunity, and cured fulminant glomerulonephritis in these recipients. These studies generated a new perspective on the potential usefulness of BM and stem cell transplants to cure major diseases that can possibly be treated by BMT. Mixed BMT from TCD BALB/c and BXSB mice cured autoimmunities and fulminant glomerulonephritis in BXSB mice. LE disease plus coronary vascular disease that occurs in (NZW x BXSB)F1 mice, along with idiopathic thrombocytopenic purpura, is also cured in lethally irradiated (NZW x BXSB)F1 mice by BMT from C57BL/6 donors. Furthermore, hemolytic anemia, autoimmune phenomena, and hyalinizing glomerular renal disease of New Zealand Black (NZB) mice were prevented or cured by stem cell transplants using purified stem cells from MHC-matched DBA/2 donors or NZB donors. Consequently, we reasoned that autoimmunities reside in stem cells. More recently, we found that transplants of both BM cells and bones can completely and permanently prevent otherwise highly resistant autoimmune diseases of MRL/lpr lpr mice and an autoimmune polyarthritis of NZB/Kn mice. Ildstad concluded that lethal preparative measures would not be acceptable for preparations to treat autoimmune diseases, so we now employ a gentle method for producing stable mixed chimerism described by Sharabi and Sachs to achieve mixed marrow transplantation and mixed hematopoietic chimerism. Other diseases we are approaching using this gentle manipulation include two forms of diabetes: insulin-dependent diabetes mellitus (IDDM) type I in NOD mice and non-insulin-dependent diabetes mellitus (NIDDM) type II in KK/Ay mice, atherosclerosis of apolipoprotein-E + kno
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PMID:Progress toward production of immunologic tolerance with no or minimal toxic immunosuppression for prevention of immunodeficiency and autoimmune diseases. 1083 46

To clarify the incidence and characteristics of hematopoietic cell transplantation (HCT)-related nephropathy (HCT-N) in Japan, we sent questionnaire letters to 188 hematologic divisions of 91 hospitals and analyzed the responses. Of 2,136 Japanese hematopoietic cell transplant recipients, 51 patients (2.4%) had HCT-N. The early-onset (</=30 days after HCT), middle-onset (31 to 120 days after HCT), and late-onset (>180 days after HCT) groups included 20, 16, and 15 patients, respectively. The early-onset group mainly consisted of patients with acute renal failure (ARF) and hemolytic uremic syndrome and/or thrombotic thrombocytopenic purpura. ARF was the dominant type in the middle-onset group. The main phenotype of the late-onset group was nephrotic syndrome, which correlated with chronic graft-versus-host disease (P=0.008). The total amounts of irradiation for patients with chronic renal failure and urinary abnormality were significantly greater than those for patients with ARF (P=0.004). The survival rate of the early-onset and middle-onset groups was 47.2%, whereas 87% of patients in the late-onset group survived (P=0.002). HCT-N is expected to become a serious and important problem in Japan because of the increasing number of HCTs from unrelated donors.
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PMID:Hematopoietic cell transplantation-related nephropathy in Japan. 1097 78

Although allogeneic transplantation can be curative for patients with sickle cell disease, the toxicity of conditioning regimens has precluded its use in adults with significant end-organ damage. Newer conditioning regimens have been developed that are less toxic and that may broaden the applicability of allogeneic transplantation in this disorder. We report two adults with end-stage sickle cell disease, who underwent allogeneic transplantation from an HLA-identical sibling donor after conditioning with fludarabine/melphalan and ATG. Both patients had been extensively transfused and one had multiple RBC antibodies. One of the patients also had end-stage renal disease, and was dialysis dependent. Engraftment occurred promptly in both patients. Both achieved 100% donor chimerism and both were free of pain crises after transplant. The first patient died of a respiratory failure related to chronic graft-versus-host disease (GVHD) on day 335 after transplantation. The second patient developed severe gastro-intestinal GVHD and TTP and died on day 147 after transplantation. Conditioning with fludarabine/melphalan and ATG followed by allogeneic stem cell transplantation resulted in prompt and reliable engraftment in adults with end-stage sickle cell disease. The incidence of severe GVHD was unacceptably high and may be related to the ethnicity of the patients or to the inflammatory state associated with pre-existing sickle cell disease.
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PMID:Fludarabine-based conditioning for allogeneic transplantation in adults with sickle cell disease. 1098 93

To determine the role of perforin-mediated cytotoxic T lymphocyte (CTL) effector function in immune regulation, we studied a well-characterized mouse model of graft-versus-host disease (GVHD). Induction of acute GVHD using perforin-deficient donor T cells (pfp-->F1) initially resulted in features of acute GVHD, e.g., engraftment of both donor CD4(+) and CD8(+) T cells, upregulation of Fas and FasL, production of antihost CTL, and secretion of both Th1 and Th2 cytokines. Despite fully functional FasL activity, pfp donor cells failed to totally eliminate host B cells, and, by 4 weeks of disease, cytokine production in pfp-->F1 mice had polarized to a Th2 response. Pfp-->F1 mice eventually developed features of chronic GVHD, such as increased numbers of B cells, persistence of donor CD4 T cells, autoantibody production, and lupuslike renal disease. We conclude that in the setting of B- and T-cell activation, perforin plays an important immunoregulatory role in the prevention of humoral autoimmunity through the elimination of both autoreactive B cells and ag-specific T cells. Moreover, an ineffective initial CTL response can evolve into a persistent antibody-mediated response and, with it, the potential for sustained humoral autoimmunity.
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PMID:Role of perforin in controlling B-cell hyperactivity and humoral autoimmunity. 1099 84

Lipoprotein glomerulopathy (LPG) is a unique renal disease characterized by intraglomerular lipoprotein thrombi associated with severe proteinuria and frequent progression to renal failure. The histologic hallmark of LPG is the presence of laminated thrombi, consisting of lipid droplet, within the lumina of dilated glomerular capillaries. The findings of thrombi consisting of lipoproteins raised the possibilities that LPG might be related to a primary abnormality in lipid metabolism. However, the precise pathogenic basis of LPG remains unresolved. It was herein found that chronic graft-versus-host disease (GVHD) induced by the transfer of Ia-incompatible spleen cells from B6.C-H2(bm12) into coisogenic C57BL/6 mice with deficiency of Fc receptor gamma chain (FcRgamma) resulted in glomerulopathy that resembled LPG. The uptake of acetylated LDL was partially decreased in peritoneal macrophages isolated from FcRgamma-deficient mice compared with wild-type mice, suggesting that partial impairment of modified LDL uptake might contribute to the development of LPG associated with chronic GVHD in FcRgamma-deficient mice. LPG has been suggested to be a disorder of primary abnormality in lipid metabolism; these findings would therefore provide novel insight into the disease process.
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PMID:Chronic graft-versus-host autoimmune disease in Fc receptor gamma chain-deficient mice results in lipoprotein glomerulopathy. 1203 82

Acute and chronic renal dysfunction are common after hematopoietic stem cell transplantation (HSCT). Although the pathology of chronic HSCT nephropathy is well described, the histologic changes that accompany acute renal dysfunction after HSCT are less well known because renal biopsies are rarely undertaken in the peritransplantation period. Archival renal tissue from consecutive HSCT recipients who died and underwent autopsy at a single center during an 8-year period was studied. Abnormalities of renal pathology were described, and associations of histologic abnormalities with clinical events were systemically studied. Abnormalities of renal histology were common among the 26 patients in this study. The 3 most common histologic abnormalities were glomerular sclerosis (19/26; 73%), tubular epithelial atypia (19/26; 73%), and tubular calcification (18/26; 69%). Tubulitis (16/24; 67%) and interstitial fibrosis (16/26; 62%) were also frequently observed. Clinical veno-occlusive disease was not associated with histologic evidence of thrombotic microangiopathy in the kidney at autopsy. Also, clinical graft-versus-host disease was not associated with renal tubulitis. Unexpectedly, the proportion of patients with tubular atrophy (54%) or interstitial fibrosis (62%) was high, considering the young age of the patients at transplantation and their normal pretransplantation creatinine clearance. Well-recognized histologic abnormalities are common in the kidneys of patients who die after HSCT. Although we did not demonstrate associations of these histologic changes with clinical variables before death, larger studies with prospectively collected renal tissue are warranted.
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PMID:Renal pathology at autopsy in patients who died after hematopoietic stem cell transplantation. 1465 51

Improving survival rates following pediatric bone marrow transplantation (BMT) will likely result in greater numbers of children progressing to end-stage renal disease (ESRD) because of prior chemotherapy, irradiation, sepsis, and exposure to nephrotoxic agents. Renal transplantation remains the treatment of choice for ESRD; however, the safety of renal transplantation in this unique population is not well established. We report our experience with living related renal transplantation in three pediatric patients with ESRD following prior BMT. Two patients with neuroblastoma and ESRD because of BMT nephropathy, and one patient with Schimke immuno-osseous dysplasia and ESRD because of immune complex mediated glomerulonephritis and nephrotic syndrome. Age at time of BMT ranged from 2 to 7 yr. All patients had stable bone marrow function prior to renal transplantation. Age at renal transplant ranged from 8 to 14 yr. All three patients have been managed with conventional immunosuppression, as no patient received a kidney and BMT from the same donor source. These patients are currently 7 months to 6 yr status post-living related transplant. All have functioning bone marrow and kidney transplants, with serum creatinine levels ranging 0.6-1.2 mg/dL. There have been no episodes of rejection. One patient with a history of grade III skin and grade IV gastrointestinal-graft-vs.-host disease (GI-GVHD) prior to transplantation, had a mild flare of GI-GVHD (grade I) post-renal transplant and is currently asymptomatic. The incidence of opportunistic infection has been comparable with our pediatric renal transplant population without prior BMT. One patient was treated for basal cell carcinoma via wide local excision. Renal transplantation is an excellent option for the treatment of pediatric patients with ESRD following BMT. Short-term results in this small population show promising patient and graft survival, however long-term follow-up is needed. Pre-existing immune system impairment and bone marrow function should be taken into consideration when weighing different immunosuppressive agents for renal transplantation. Patients who have undergone renal transplantation following BMT are at high risk for opportunistic infections and malignancy, and need life-long medical surveillance.
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PMID:Successful renal transplantation following prior bone marrow transplantation in pediatric patients. 1536 89

Bone marrow transplantation (BMT) is an effective therapeutic strategy for leukaemic malignancies and depressed bone marrow following cancer. However, its side effects on kidneys have been reported. Some drugs and irradiation are also suggested to be nephrotoxic. It is well known that haemolytic uraemic syndrome (HUS) after BMT develops as late-onset BMT nephropathy. Cyclosporine A (CsA) is a possible cause. Radiation nephropathy shows changes that are similar to the histology of HUS. These findings suggest that endothelial damage is closely associated with the pathogenesis of post-BMT nephropathy. Recently, some patients have developed glomerulonephritis accompanied by graft-versus-host disease (GVHD) after BMT. In these patients immune deposits are found mainly in subepithelium and mesangium equal to those of secondary membranous glomerulonephritis. A murine experimental model of GVHD manifests similar symptoms and histological changes to those of actual patients and may suggest the pathogenesis of glomerulonephritis.
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PMID:Renal involvement in bone marrow transplantation. 1622 Nov 8

Graft-versus-host disease (GVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (HSCT), but membranous glomerulopathy (MG) has rarely been described as a manifestation of chronic GVHD. We report two cases of MG in children who underwent allogeneic HSCT. The clinical findings were characterized by edema of the lower extremities and nephrotic proteinuria in one case and hypertension, hematuria and edema with non-nephrotic proteinuria in the other one. Renal biopsy was consistent with MG and appropriate immunosuppressive therapy was prescribed. Both patients achieved complete remission and are alive without renal disease 4 and 2 years after the diagnosis of MG. The normal levels of albumin and non-nephrotic proteinuria in one of the two cases raise the question of whether the real incidence of MG after HSCT is underestimated. Therefore, we strongly suggest regular urine analysis during the follow-up of children undergoing HSCT in order to diagnose MG early.
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PMID:Membranous glomerulopathy in children given allogeneic hematopoietic stem cell transplantation. 1626 22

Lipoprotein glomerulopathy (LPG) is a unique entity of renal lipidosis characterized by peculiar histopathologic characteristics of lipoprotein thrombi and an abnormal plasma lipoprotein profile resembling type III hyperlipoproteinemia, with a marked increase in serum apolipoprotein E (apoE) concentrations. At present, 65 cases have been reported worldwide, although most patients are found in Japan and east Asian countries. Recently, we identified 4 types of novel apoE mutations associated with LPG. In particular, a mutation designated apoE Sendai, in which arginine 145 is substituted with proline, occurs in the majority of Japanese patients. The virus-mediated transduction of apoE Sendai resulting in the development of LPG in apoE-deficient mice confirms the etiologic role of apoE mutation in LPG. Conversely, experimental graft-versus-host disease induced in Fc receptor gamma-chain-deficient mice showed LPG-like lesions in glomeruli without apoE mutations. Considered together, we believe that intrinsic factors in the kidney also contribute to the induction of LPG. Today, apoE and related lipid abnormalities are reported to have an important role in the development of various renal diseases, eg, diabetic nephropathy and immunoglobulin A nephropathy. In this article, we review clinical and histopathologic features of LPG, describe the etiologic role of apoE variants and intrinsic renal factors, and discuss the impact of LPG on mechanisms of other renal diseases.
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PMID:Impact of lipoprotein glomerulopathy on the relationship between lipids and renal diseases. 1643 Dec 49


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